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Modulation of the myeloid compartment of the immune system by angiogenic- and kinase inhibitor-targeted anti-cancer therapies

  • Focussed Research Review
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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Targeted therapies were rationally designed to inhibit molecular pathways in tumor cells critically involved in growth and survival; however, many drugs used in targeted therapies may affect the immune system. In addition, selected conventional chemotherapeutic agents have also been reported to be endowed with direct or indirect effects on immunity, for instance via immunogenic death of tumors. Thus, cancer therapies may have off-target effects, some of which are directed to the immune system. Here, we will review some of these effects in specific therapeutic approaches. We will examine the modulation of the immune contexture in human sarcoma and melanoma induced by anti-angiogenic therapies and by BRAF inhibitors, respectively. We will then discuss how the anti-tumor agent trabectedin is selectively cytotoxic to cells of the monocytic-macrophage lineage and how these immune-related effects can be part of the response to treatment.

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Abbreviations

ASPS:

Alveolar soft part sarcoma

DC:

Dendritic cells

GIST:

Gastrointestinal stromal tumor

M/DSFT:

Malignant and dedifferentiated solitary fibrous tumors

M-CSF:

Monocyte-colony stimulating factor

MDSC:

Myeloid-derived suppressive cells

PDGFR:

Platelet-derived growth factor receptor

TAM:

Tumor-associated macrophages

TRAIL:

Tumor necrosis factor-related apoptosis-inducing ligand

Treg:

Regulatory T cells

VEGFR:

Vascular endothelial growth factor receptor

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Acknowledgments

This study was supported by the Associazione Italiana Ricerca sul Cancro (CC IG-10615; LR IG-10727; MR IG-9030 and PA IG-12051). M. Tazzari and C. Belgiovine are supported by a fellowship from FIRC (Fondazione Italiana Ricerca sul Cancro).

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No conflict of interest to declare.

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Authors and Affiliations

  1. Unit of Immunotherapy of Human Tumor, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    Chiara Castelli, Licia Rivoltini, Monica Rodolfo & Marcella Tazzari

  2. Department of Immunology and Inflammation, Clinical and Research Institute Humanitas, Via Manzoni 113, Rozzano, 20089, Milan, Italy

    Cristina Belgiovine & Paola Allavena

Authors
  1. Chiara Castelli
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  2. Licia Rivoltini
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  3. Monica Rodolfo
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  4. Marcella Tazzari
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  5. Cristina Belgiovine
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  6. Paola Allavena
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Corresponding author

Correspondence to Paola Allavena.

Additional information

This paper is a Focussed Research Review based on a presentation given at the Eleventh Meeting of the Network Italiano per la Bioterapia dei Tumori (NIBIT) on Cancer Bio-Immunotherapy, held in Siena, Italy, 17th–19th October 2013. It is part of a CII series of Focussed Research Reviews and meeting report.

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Castelli, C., Rivoltini, L., Rodolfo, M. et al. Modulation of the myeloid compartment of the immune system by angiogenic- and kinase inhibitor-targeted anti-cancer therapies. Cancer Immunol Immunother 64, 83–89 (2015). https://doi.org/10.1007/s00262-014-1576-1

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  • DOI: https://doi.org/10.1007/s00262-014-1576-1

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